The present invention relates to isocyanoalkylcarbonic acid derivatives, to the reaction therof in isocyanide multi-component reactions to form sec-amidoalkylcarbonic acid derivatives, and to those sec-amidoalkylcarbonic acid derivatives. 
Many commercially interesting, organic substances (e.g. pharmacological active ingredients and natural substances) contain structural features that are derived from xcex1-hydroxycarboxylic acid derivatives or xcex1-aminocarboxylic acid derivatives. The synthesis of those substances is often a complex procedure. Using isocyanide multicomponent reactions (isocyanide MCRs), such as the Passerini reaction (P-3CR) and the various variants of the Ugi reaction, it is possible to prepare those complicated structural features in a simple manner [I. Ugi et al. in: Comprehensive Organic Synthesis: Selectivity for Synthetic Efficiency, Vol. II, B. M. Trost, C. H. Heathcock, Pergamon Press, Oxford, 1991].
In multicomponent reactions, three or more starting materials (components) can be reacted with one another simultaneously or almost simultaneously in a one-pot reaction without the need to work up intermediates. The group of isocyanide MCRs (one component is an isocyanide) includes, for example, the Passerini 3-component reaction (P-3CR); the Ugi 4-component reaction (U-4CR) [I. Ugi, Angew. Chem. 1962, 74, 9]; and the Ugi 5-centre 4-component reaction (U-5C-4CR) [I. Ugi et al., Angew. Chem. 1996, 108, 185] and the Ugi 4-component reaction with xcex2-amino acids (U-4CR/xcex2-AS) [I. Ugi et al., Tetrahedron 1995, 51, 139].
The products of those four types of reaction have secondary amide functions that are very difficult to convert into other derivatives, such as carboxylic acids and carboxylic acid esters, without the remainder of the molecule or any stereo-centres present being destroyed at the same time. The carbon atom of the secondary amide function that is formed originates from the isocyanide component used (RIso-NC). 
It is therefore a problem of the present invention to provide new isocyanide MCR products (sec-amidoalkylcarbonic acid derivatives), the secondary amide function of which can be converted into commercially interesting products (pharmacological sub-structures), such as xcex1-hydroxycarboxylic acid derivatives or xcex1-aminocarboxylic acid derivatives, under very mild reaction conditions.
A further problem of the present invention is to provide processes and intermediates for the preparation of the isocyanide MCR products.
The problem is solved by compounds (isocyanoalkylcarbonic acid derivatives) of the general formula I 
The isocyanoalkylcarbonic acid derivatives I are at least bifunctional molecules in which an isocyanide function and a carbonic acid derivative function are bonded to one another via a bridge A having a chain length of 2 or 3 carbon atoms. It is particularly significant that the compound I contains only one isocyanide function: the cleavage of sec-amidoalkylcarbonic acid derivatives that would be obtained from isocyanide MCRs with diisocyanoalkylcarbonic acid derivatives would result in non-uniform products.
In formula I
A is a group of the formula 
Z may be an O atom or a S atom, preferably an O atom.
The radicals R1 to R4 and, when present, R6 and R7 each have a maximum of 20 carbon atoms and are independently of one another H atoms, substituted or unsubstituted alkyl, alkenyl, alkynyl, alkaryl, aryl, alicyclic radicals, heteroalicyclic or heteroaryl radicals having up to 4 hetero atoms (hetero atoms are O, N, S); preferably those radicals each have a maximum of 15 carbon atoms, especially a maximum of 10 carbon atoms, and are independently of one another H atoms, substituted or unsubstituted alkyl, alkenyl, alkynyl, alicyclic or aryl radicals, more especially H atoms, substituted or unsubstituted methyl, ethyl, propyl, butyl, pentyl, hexyl, benzyl and cyclohexyl radicals, and most especially H atoms, methyl, ethyl, propyl, butyl, pentyl, hexyl, benzyl and cyclohexyl radicals.
Two of the radicals R1 to R4 and, when present, R6 and R7 that are separated from one another by up to two carbon atoms (such as, for example, the radicals R1 and R2, R3 and R4, R1 and R3 or R6 and R7, but not, for example, R1 and R6, since the latter are separated from one another by three carbon atoms) may be constituents of a common ring system, the ring system comprising a substituted or unsubstituted alicyclic monocycle (5 to 8 ring atoms), a heteroalicyclic monocycle (5 to 8 ring atoms with 0, 1 or 2 hetero atoms [O, N, S]), an alicyclic bicycle (7 to 14 ring atoms) or a heteroalicyclic bicycle (7 to 14 ring atoms with up to 4 hetero atoms [O, N, S]), preferably a substituted or unsubstituted alicyclic monocycle (5 to 8 ring atoms) or an alicyclic bicycle (7 to 14 ring atoms), more especially a cyclopentyl, cyclohexyl, norbornyl or bornyl ring.
The radical R5 has a maximum of 20 carbon atoms, preferably 15 carbon atoms, especially 10 carbon atoms, and is a substituted or unsubstituted alkyl, alkenyl, alkynyl, allyl, alkaryl, aryl, alicyclic radical, heteroalicyclic or heteroaryl radical having up to 4 hetero atoms (hetero atoms are O, N, S), preferably an allyl, benzyl, 2-bromoethyl, n-butyl, 2-chloroethyl, 1-chloroethyl, chloromethyl, ethyl, 1-(9-fluorenyl)-ethyl, 9-fluorenylmethyl, isobutyl, menthyl, 4-methoxycarbonylphenyl, 4-methoxyphenyl, methyl, 4-nitrobenzyl, 2-nitrophenyl, 4-nitrophenyl, 4,5-dimethoxy-2-nitrobenzyl, phenyl, 2,2,2-trichloro-tert-butyl, 2,2,2-trichloroethyl, vinyl, 4-methylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, xcex1-chloro-(trifluoromethyl)benzyl, 3-tert-butylphenyl, 2,4,6-trichlorophenyl, pentafluorophenyl, 2-(p-toluenesulfonyl)ethyl, diphenylmethyl, 2-(trimethylsilyl)ethyl, methoxymethyl, methylthiomethyl, (2-trimethylsilyl)ethoxymethyl, benzyloxymethyl or (2-methoxy)ethyloxymethyl radical.
If desired, the compounds of the formula I may be bonded to a solid phase (resin) via one or more of the radicals R1 to R4 and, when present, R6 and R7, also R5 or Z. Suitable resins are, for example, any conventional resins that are used in organic solid phase synthesis, such as, for example, polystyrene/divinyl benzene, polyethylene glycol or polyethylene glycol/polystyrene resins.
The radicals R1 to R4 and, when present, R6 and R7 and also R5, as well as ring systems formed from those radicals, may be substituted by one, two, three or more, preferably a maximum of one, of the following groups: halogen, tert-amino, nitro, cyano, ether, silyloxyalkyl, thioether, carboxylic acid ester, tert-carboxylic acid amide, carboxylic acid imide, silyl, sulfonic acid ester, sulfenic acid ester, sulfinic acid ester and tert-sulfonamido functions.
The substituents of the radicals R1 to R4 and, when present, R6 and R7 may, for example, increase the acidity of the H atom in the xcex1-position to the isocyanide function and thus make it possible to use weak bases in the synthesis of the compound I. The choice of the radicals R1 to R7 is not essential for the suitability of the compound I for use in the isocyanide MCRs and the subsequent cleavage (see below), but they may be used, for example, to steer the solubility behaviour of the isocyanoalkylcarbonic acid derivatives or the cyclic urethanes formed in the cleavage.
A may especially be a group of the formula xe2x80x94C(CH3)2xe2x80x94CH2xe2x80x94.
Preferred compounds of the formula I are:
(2-isocyano-2-methyl)-propyl-1-carbonic acid allyl ester,
(2-isocyano-2-methyl)-propyl-1-carbonic acid benzyl ester,
(2-isocyano-2-methyl)-propyl-1-carbonic acid (4-nitrobenzyl) ester,
(2-isocyano-2-methyl)-propyl-1-carbonic acid ethyl ester,
(2-isocyano-2-methyl)-propyl-1-carbonic acid phenyl ester,
(2-isocyano-2-methyl)-propyl-1-carbonic acid (4-nitrophenyl) ester,
(2-isocyano-2-methyl)-propyl-1-carbonic acid vinyl ester,
(2-isocyano-2-methyl)-propyl-1-carbonic acid (2,2,2-tri-chloroethyl) ester,
(2-isocyano-2-methyl)-propyl-1-carbonic acid (2-trimethyl-silyl-ethyl) ester,
(2-isocyano-2-methyl)-propyl-1-carbonic acid methyl ester,
(1-isocyano-2-methyl)-propyl-2-carbonic acid allyl ester,
(1-isocyano-2-methyl)-propyl-2-carbonic acid benzyl ester,
(1-isocyano-2-methyl)-propyl-2-carbonic acid (4-nitrobenzyl) ester,
(1-isocyano-2-methyl)-propyl-2-carbonic acid ethyl ester,
(1-isocyano-2-methyl)-propyl-2-carbonic acid phenyl ester,
(1-isocyano-2-methyl)-propyl-2-carbonic acid (4-nitrophenyl) ester,
(1-isocyano-2-methyl)-propyl-2-carbonic acid vinyl ester,
(1-isocyano-2-methyl)-propyl-2-carbonic acid (2,2,2-tri-chloroethyl) ester,
(1-isocyano-2-methyl)-propyl-2-carbonic acid (2-trimethyl-silyl-ethyl) ester,
(1-isocyano-2-methyl)-propyl-2-carbonic acid methyl ester.
Also provided are processes for the preparation of compounds of the general formula I.
A process is characterised in that an isocyanoalkyl alcoholate anion CNxe2x80x94CR1R2xe2x80x94CR3R4xe2x80x94Oxe2x88x92 or CNxe2x80x94CR1R2xe2x80x94CR3R4xe2x80x94CR6R7xe2x80x94Oxe2x88x92 is reacted with a haloformic acid derivative Xxe2x80x94COxe2x80x94Zxe2x80x94R5, for example in an aprotic solvent, such as THF, Et2O, DME or CH2Cl2, to form a corresponding isocyanoalkylcarbonic acid derivative of the formula I, for example in accordance with the following scheme: 
The isocyanoalkyl alcoholate anions may be prepared either from the corresponding isocyanoalkyl alcohols or from the cyclic imido esters (2-oxazoline or 2-oxazine) by reaction with a base (such as, for example, n-BuLi), as described in the literature [D. Hoppe, Angew. Chem. 1974, 86, 878].
The 2-oxazolines or 2-oxazines can readily be prepared from the corresponding 2-aminoethanols or 3-aminopropanols by reaction with formic acid [A. I. Meyers et al., Tetrahedron 1994, 50, 2297] or dimethylformamide dimethyl acetal [A. I. Meyers et al., J. Org. Chem. 1991, 56, 1961].
The required isocyanides may be prepared either from the corresponding amines by reaction with chloroform and strong bases, such as, for example, alkali metal hydroxide (carbylamine reaction) [I. Ugi et al in: xe2x80x9cIsonitrile Chemistryxe2x80x9d, I. Ugi (ed.), Academic Press, New York., 1971] or from the corresponding formamides by reaction with POCl3 or phosgene [I. Ugi et al., Angew. Chem. 1965, 77, 492] in the presence of nitrogen bases.
A further process for the preparation of compounds of the general formula I is characterised in that a formamidoalkylcarbonic acid derivative OCHxe2x80x94NHxe2x80x94CR1R2xe2x80x94CR3R4xe2x80x94Oxe2x80x94COxe2x80x94Zxe2x80x94R5 or OCHxe2x80x94NHxe2x80x94Cr1R2xe2x80x94CR3R4xe2x80x94CR6R7xe2x80x94Oxe2x80x94COxe2x80x94Zxe2x80x94R5 is converted, for example, in an aprotic solvent, such as CH2Cl2, by removal of water into a corresponding isocyanoalkylcarbonic acid derivative of the formula I, for example in accordance with the following scheme. 
The removal of water may be effected, for example, by reaction with phosgene or di- or tri-phosgene or phosphorus oxychloride in the presence of nitrogen bases [I. Ugi et al., Angew. Chem. 1965, 77, 492].
The formamidoalkylcarbonic acid derivatives may be obtained by reaction of chloroformic acid derivatives with formamidoalkyl alcohols, which may in turn be prepared from the commercially available aminoalkyl alcohols by reaction with formic acid methyl ester.
Both processes are also suitable for the preparation of isocyanoalkylcarbonic acid derivatives that are bonded to a solid phase (resin) via one or more of the radicals R1 to R4 and, when present, R6 and R7, also R5 or Z, for example to resins that are derivatised with a carbonyl function. Such resins are commercially available. In the process there are used, for example, resin-bonded chloroformic acid esters or isocyanides that can be prepared by derivatisation of OH-functionalised or SH-functionalised resins with phosgene [G. Skorna, I. Ugi, Chem. Ber. 1978, 111, 3965] or isocyanoalkylmethyl esters. The removal of water from correspondingly used resin-bonded formamides can also be carried out without problems [Mjalli A. M. M. et al., Tetrahedron Lett. 1996, 37, 1149].
All processes are also suitable for the preparation of chiral isocyanoalkylcarbonic acid derivatives.
Isocyanide Multicomponent Reactions
A multicomponent reaction is understood as being a reaction in which the product is formed from at least three different starting materials and contains substantial parts of those starting materials.
It is characteristic of isocyanide MCRs that in the course of such MCRs the two-bond carbon atom of the isocyanide function is converted in an intramolecular rearrangement, irreversibly and with energy being released, into a four-bond carbon atom of a secondary amide function. This constitutes the thermodynamic driving force of the isocyanide MCRs. This driving force has the effect that the intramolecular rearrangement takes place independently of the steric requirements of the substituents in question, so that virtually any substituents can be used. As a result, it is possible for an enormous range of acid, carbonyl, isocyanide and if applicable amine components to be used in the isocyanide MCRs. For that reason, isocyanide MCRs are the subject of intensive research in combinatorial chemistry where the aim is to prepare many different molecules in a one-pot synthesis [F. Balkenhohl, Angew. Chem. 1996, 108, 2463]. A large number of different Passerini and Ugi products have been prepared and described in the literature [I. Ugi, S. Lohberger, R. Karl in: Comprehensive Organic Synthesis: Selectivity for Synthetic Efficiency, Vol. II, B. M. Trost, C. H. Heathcock, Pergamon Press, Oxford, 1991; I. Ugi, Angew. Chem. 1962, 74, 9].
Using the isocyanide MCRs it is possible for complicated molecules to be synthesised simply and rapidly in a one-pot synthesis. The advantages over the customary multi-stage preparation methods are savings in time, savings in materials, higher yields with fewer secondary products and consequently reduced outlay for purification. The disadvantage of conventional isocyanide MCR products is that the secondary amide bond formed from the isocyanide cannot be modified or can be modified only in certain systems or only under drastic conditions.
The isocyanide MCRs can be carried out in a temperature range of from xe2x88x9290xc2x0 C. to 90xc2x0 C., preferably from 40xc2x0 C. to 40xc2x0 C. At low temperatures the MCRs proceed more slowly, while at too high a temperature the isocyanide may be destroyed.
Suitable solvents are any inert solvents that do not react or react only very slowly with the components used, such as, for example, lower alcohols, CH2Cl2, hexane, trifluoroethanol, THF or CH3CN.
The reaction times may range from a few minutes to a few weeks.
The concentration range of the components may be from 0.01 molar to 10 molar, preferably from 0.1 to 2 molar. If the concentration is too low, the isocyanide MCRs proceed only very slowly, while too high a concentration may lead to secondary reactions. The components are preferably used in equimolar amounts, but it is also possible to use individual components in excess, since the resulting MCR products do not react further with the components used.
Also disclosed according to the invention are sec-amidoalkyl-carbonic acid derivatives of the formulae III to IX and processes for the preparation thereof. 
In the formulae III to IX, the radicals are defined as follows:
Z, A and the radical R5 are as defined above;
the radicals RA, RB, RC, RD, RAs1, RAs2, RE, RF, RG, RH, RB1 and RB2 each have a maximum of 20 carbon atoms and are independently of one another H atoms or unsubstituted alkyl, alkenyl, alkynyl, alkaryl, aryl, alicyclic radicals, heteroalicyclic or heteroaryl radicals having up to 6 hetero atoms (hetero atoms are O, N, S) or are corresponding radicals that are substituted by one, two, three or more halogen, tertamino, nitro, cyano, carboxylic acid ester, carboxylic acid amide, carboxylic acid imide, alkyloxy, epoxy, boron, silyloxy, silyl, thio, sulfonic acid ester, sulfenic acid ester, sulfinic acid ester, sulfonamido, urethane or urea functions, or RB is a group of the formula OH, RRxe2x80x2Nxe2x80x94 (wherein R and Rxe2x80x2 may each independently of the other have the same definitions as RA but are independent thereof) or is a 1-aminocarbohydrate radical O-protected by C1-C6alkyl or by C1-C6alkylcarbonyl; preferably those radicals each have a maximum of 10 carbon atoms and are as defined above.
RNu is a group of the formula HOxe2x80x94, RAlkOxe2x80x94 or RAm1RAm2Nxe2x80x94, wherein RAlk is a methyl, ethyl, propyl, butyl, allyl or benzyl radical and RAm1 and RAm2 are C1-C6alkyl radicals, or RAm1 and RAm2 are constituents of a 5- or 6-membered cycloalkyl ring or 6-membered cycloalkyl ring having a further hetero atom (N, O).
Generally, the radicals Rs1A, RB, RC, RD, RAs1, RAs2, RE, RF, RG, RH, RB1, RB2, R and Rxe2x80x2 may be substituted by any functional groups that do not react or react only very slowly with the functional groups of the isocyanide MCR components, see, for example, [I. Ugi, S. Lohberger, R. Karl in: Comprehensive Organic Synthesis: Selectivity for Synthetic Efficiency, Vol. II, B. M. Trost, C. H. Heathcock, Pergamon Press, Oxford, 1991; I. Ugi, Angew. Chem. 1962, 74, 9]. For example, aldehyde ketones may be used in the U-4CR, in which case when all the components are used in equimolar amounts only the aldehyde function reacts in the U-4CR as a result of its higher reactivity.
Sec.-amidoalkylcarbonic Acid Derivatives of the Formulae III and IV
In the Passerini reaction [M. Passerini, Gazz. Chim. Ital., 1921, 51 (11); I. Hagedorn, U. Eholzer, Chem. Ber. 1965, 98, 936], an acid component, a carbonyl component (aldehyde or ketone) and an isocyanide component are used in a multicomponent reaction to synthesise xcex1-acyloxyamides or xcex1-hydroxyamides, for example in accordance with the following scheme. 
If a carbonyl component RCxe2x80x94COxe2x80x94RD, the isocyanoalkylcarbonic acid derivative of the formula I and a carboxylic acid (RAxe2x80x94COOH) as acid component are reacted in the P-3CR, the sec-amidoalkylcarbonic acid derivative III is formed; using water as acid component the Sec-amidoalkylcarbonic acid derivative IV is formed. 
Preparation of Sec-amidoalkylcarbonic Acid Derivatives of the Formulae III and IV by Means of P-3CR
A carboxylic acid RAxe2x80x94COOH or water is reacted with a carbonyl component RCxe2x80x94COxe2x80x94RD and the isocyanoalkylcarbonic acid derivative of the formula I in a P-3CR. The reaction can be carried out, for example, as described in the literature [M. Passerini, Gazz. Chim. Ital., 1921, 51 (11); I. Hagedorn, U. Eholzer, Chem. Ber. 1965, 98, 936].
Sec.-amidoalkylcarbonic Acid Derivatives of the Formulae V, VI and VII
In the U-4CR, the use of an acid component, for example carboxylic acid or water, a carbonyl component, an amine component (e.g. primary or secondary amine) and an isocyanide component yields xcex1-aminoacylamides or xcex1-aminoamides, for example in accordance with the following scheme: 
If a carbonyl component RCxe2x80x94COxe2x80x94RD, the isocyanoalkylcarbonic acid derivative of the formula I, a carboxylic acid (RAxe2x80x94COOH) and a primary amine (RBxe2x80x94NH2) are used in the U-4CR, the sec-amidoalkylcarbonic acid derivative V is formed; using water as acid component and a primary amine (RBxe2x80x94NH2), the sec-amidoalkylcarbonic acid derivative VI is formed. If a carbonyl component RCxe2x80x94COxe2x80x94RD, the isocyanoalkylcarbonic acid derivative of the formula I, a secondary amine (RB1xe2x80x94NHxe2x80x94RB2) and water as acid component are used in the U-4CR, the sec-amidoalkylcarbonic acid derivative VII is formed. 
As amine components there may be used ammonia, primary amines, O-acylated or O-alkylated 1-aminocarbohydrates, hydroxylamines [NH2OH] or hydrazines [H2NNR(Rxe2x80x2)] and derivatives thereof.
As carbonyl components there are suitable both aldehydes (including sterically demanding aldehydes) and ketones (except for diarylketones). Occasionally pre-condensation of the imine is necessary.
The sec-amidoalkylcarbonic acid derivatives of the formulae V, VI and VII may be used, for example, to prepare N-acyl-xcex1-amino acid derivatives, N-acyl-N-alkyl-xcex1-amino acid derivatives or N,Nxe2x80x2-dialkyl-xcex1-amino acid derivatives.
Preparation of the Sec-amidoalkylcarbonic Acid Derivatives of the Formulae V, VI and VII by Means of U-4CR
A carboxylic acid RAxe2x80x94COOH or water is reacted with a carbonyl component RCxe2x80x94COxe2x80x94RD, an amine component RBxe2x80x94NH2 or RB1xe2x80x94NHxe2x80x94RB2 and the isocyanoalkylcarbonic acid derivative of the formula I in an Ugi 4-component reaction. The reaction may be carried out, for example, as described in the literature [I. Ugi et al., Chem. Ber. 1961, 94, 2802].
Monocyclic Sec-amidoalkylcarbonic Acid Derivatives of the Formula VIII
The synthesis of monocyclic sec-amidoalkylcarbonic acid derivatives of the formula VIII by means of U-4CR/xcex2-AS represents a variant of the U-4CR in which both the amine component and the acid component are present in a single starting material, a xcex2-amino acid. The xcex2-amino acid is reacted with a carbonyl component and an isocyanide component in a U-4CR/xcex2-AS, for example in accordance with the following scheme: 
In that reaction, when a carbonyl component RCxe2x80x94COxe2x80x94RD, the isocyanoalkylcarbonic acid derivative of the formula I and a xcex2-amino acid H2Nxe2x80x94CRERFxe2x80x94CRGRHxe2x80x94COOH are used, the sec-amidoalkylcarbonic acid derivative VIII is formed as reaction product. 
Preparation of Monocyclic Sec-amidoalkylcarbonic Acid Derivatives of the Formula VIII by Means of U-4CR/xcex2-As
A xcex2-amino acid H2Nxe2x80x94CRERFxe2x80x94CRGRHxe2x80x94COOH is reacted with a carbonyl component RCxe2x80x94COxe2x80x94RD and the isocyanoalkylcarbonic acid derivative of the formula I in a U-4CR/xcex2-As. The reaction may be carried out, for example, as described in the literature [I. Ugi et al., Tetrahedron 1995, 51, 139].
Sec.-amidoalkylcarbonic Acid Derivatives of the Formula IX
The U-5C-4CR is a well-known variant of the U-4CR and is used for the preparation of 1,1xe2x80x2-iminodicarboxylic acid derivatives [W. Hxc3x6rl, Dissertation, Technische Universitxc3xa4t Mxc3xcnchen, 1996]. In the U-5C-4CR, an xcex1-amino acid, a carbonyl component, an isocyanide component and a nucleophile, which may be an alcohol, a secondary amine or water, are reacted, for example, according to the following scheme: 
If RNuxe2x80x94H is an alcohol or water, then it is used in excess. In the U-5C-4CR, when an xcex1-amino acid H2Nxe2x80x94CRAs1RAs2xe2x80x94COOH, a carbonyl component RCxe2x80x94COxe2x80x94RD, the isocyanoalkylcarbonic acid derivative of the formula I and a nucleophile RNuxe2x80x94H are used, the sec-amidoalkylcarbonic acid derivative IX is formed. 
Preparation of Sec-amidoalkylcarbonic Acid Derivatives of the Formula IX by Means of U-5C-4CR
An xcex1-amino acid H2Nxe2x80x94CRAs1RAs2xe2x80x94COOH is reacted with a carbonyl component RCxe2x80x94COxe2x80x94RD, the isocyanoalkylcarbonic acid derivative of the formula I and a nucleophile RNuxe2x80x94H in an Ugi-5C-4CR. The reaction may be carried out, for example, as described in the literature [I. Ugi et al., Tetrahedron, 1996, 52, 11657].
If, for example, RNUxe2x80x94H is an alcohol, then an xcex1-amino acid, a carbonyl component and the isocyanoalkylcarbonic acid derivative I are dissolved or suspended in an alcohol, which is the solvent and the nucleophile simultaneously, and stirred. When the reaction is complete, the solvent is removed and, if necessary, the reaction product is purified.
If, for example, RNuxe2x80x94H is a secondary amine, then an xcex1-amino acid, a carbonyl component, the isocyanoalkylcarbonic acid derivative I and a secondary amine are dissolved or suspended in a solvent/water mixture, such as, for example, a THF/H2O mixture, and stirred. When the reaction is complete, the solvent is removed and, if necessary, the reaction product is purified.
If, for example, RNUxe2x80x94H is water, then an xcex1-amino acid, a carbonyl component and the isocyanoalkylcarbonic acid derivative I are dissolved or suspended in a solvent/water mixture, such as, for example, a THF/H2O mixture, and stirred. When the reaction is complete, the solvent is removed and, if necessary, the reaction product is purified.
Cleavage of the Secondary Amide Bond of the Sec-amidoalkylcarbonic Acid Derivatives of the Formulae III to IX
It is also possible for the novel sec-amidoalkylcarbonic acid derivatives of the formulae III to IX to be converted without difficulty into xcex1-hydroxycarboxylic acid derivatives or xcex1-aminocarboxylic acid derivatives by reaction with a base.
By reaction of the sec-amidoalkylcarbonic acid derivatives with a base, the secondary amide proton is abstracted. Suitable bases are, for example, mild, non-nucleophilic bases, such as, for example, potassium tert-butanolate, alkali metal hydroxide, alkali metal hydride or nitrogen bases, such as lithium diisopropylamine or 1,5-diazabicyclo-[4.3.0]non-5-ene, for example in an aprotic solvent, such as, for example, THF, Et2O or CH2Cl2. The reaction may be carried out at temperatures of from xe2x88x9280xc2x0 C. to 80xc2x0 C. By subsequent intramolecular ring closure, for example in accordance with the following scheme, there are prepared primary cleavage products X that have a cyclic N-acylurethane function. 
The radical RMCR defines the structures that are synthesised by the P-3CR, the U-4CR, the U-4CR/xcex2-As and the U-5C-4CR. In the ring closure, Zxe2x80x94R5 is removed in the form of an alcoholate or thiolate anion. The further course of the reaction is dependent on the structure of R5. If R5 is a radical that reduces the nucleophilicity of the Z function (e.g. an electrophilic radical, such as, for example, a phenyl radical), then X is capable of being isolated. If R5 is a radical that increases the nucleophilicity of the Z function (e.g. an electron-donating radical, such as, for example, an alkyl radical), then X is not capable of being isolated, but reacts in situ with the alcoholate or thiolate formed by the intramolecular ring closure to yield the corresponding ester or thioester (RMCRxe2x80x94COxe2x80x94Zxe2x80x94R5), for example in accordance with the following scheme. 
In that way it is possible to convert the secondary amide bond of the sec-amidoalkylcarbonic acid derivatives of the formulae III to IX directly into the corresponding ester. For example, by the selection of the appropriate radical R5 it is possible for the carboxyl-protecting groups known from the literature [E. Haslam, Tetrahedron 1980, 36, 2409] to be introduced directly into the isocyanoalkylcarbonic acid derivatives in a one-pot synthesis.
As mentioned above, X is capable of being isolated when R5 is a radical, such as, for example, a phenyl radical, that reduces the nucleophilicity of the Z function. As a result of its reduced nucleophilicity, caused by the aromatic mesomerism, the phenolate, for example, is not able to attack X nucleophilically and thus form the phenyl ester. This offers the possibility of isolating the corresponding primary cleavage product X and then reacting it with a nucleophile, such as an alcoholate, thiolate, hydroxyl or amino anion, for example in accordance with the following scheme, in order to obtain the corresponding esters, thioesters, amides or carboxylic acids. 
Since the process according to the invention for the cleavage of secondary amide bonds also takes place under mild basic conditions, the secondary amide bonds of the sec-amidoalkylcarbonic acid derivatives may be cleaved to yield the acetidinone ring.
In summary it may be said that all sec-amidoalkylcarbonic acid derivatives that can be prepared using the novel isocyanoalkylcarbonic acid derivatives can be reacted to form the corresponding xcex1-hydroxycarboxylic acid derivatives or xcex1-aminocarboxylic acid derivatives, because the method of cleavage is independent of the structure of the remainder of the molecule.
Cleavage Procedure for the Sec-amidoalkylcarbonic Acid Derivatives
The sec-amidoalkylcarbonic acid derivatives of the formulae III to IX are reacted with a base. For example, the sec-amidoalkylcarbonic acid derivative is dissolved in an inert, aprotic solvent, such as, for example, THF, Et2O or CH2Cl2, and a base, such as, for example, potassium tert-butanolate, is added. When the reaction is complete, the solvent is removed and the reaction product, which according to the structure of the radical R5 and the nature of the base used may be the primary cleavage product X, an xcex1hydroxycarboxylic acid derivative or an xcex1aminocarboxylic acid derivative, is purified.